Bleeding Risk Stratification Research Articles

Validation of the Valve Academic Research Consortium High Bleeding Risk Definition in Patients Undergoing TAVR.

Background: The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk (HBR) in patients undergoing transcatheter aortic valve replacement (TAVR). The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale TAVR population. Methods: Multicenter study including 10,449 patients undergoing TAVR. Based on consensus, twenty-one clinical and laboratory criteria were identified and classified as major or minor. Patients were stratified as at low, moderate, high, and very high bleeding risk according to VARC-HBR definition. The primary endpoint was the rate of BARC type 3 or 5 bleeding at 1 year, defined as the composite of peri-procedural (within 30 days) or late (after 30 days) bleeding. Results: Patients with at least one VARC-HBR criterion (n=9,267, 88.7%) had a higher risk of BARC 3 or 5 bleeding, proportional to the severity of risk assessment (10.8%, 16.1%, and 24.6% for moderate, high, and very high-risk groups, respectively). However, a comparable rate of bleeding events was observed in the low-risk and moderate-risk groups. The area under ROC curve was 0.58. Patients with VARC-HBR criteria also exhibited a gradual increase in 1-year all-cause mortality, with an up to 2-fold increased mortality risk for high and very high-risk groups (HR: 1.33, 95% CI: 1.04-1.70; and HR: 1.97, 95% CI: 1.53-2.53, respectively). Conclusions: The VARC-HBR consensus offered a pragmatic approach to guide bleeding risk stratification in TAVR. The results of the present study would support the predictive validity of the newly definition and promote its application in clinical practice to minimize bleeding risk and improve patient outcomes.

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Capsule Endoscopy for the Risk Stratification and Management of Acute Upper Gastrointestinal Bleeding in Emergency Departments: A Systematic Review on Triage, Risk Stratification, and Management

Capsule Endoscopy for the Risk Stratification and Management of Acute Upper Gastrointestinal Bleeding in Emergency Departments: A Systematic Review on Triage, Risk Stratification, and Management

Gastrointestinal Bleeding After Percutaneous Coronary Intervention: Incidence, Risk Factors, and Outcomes.

Percutaneous coronary intervention (PCI) is a well-established method for treating coronary artery disease. However, stent implantation necessitates the use of antiplatelet agents, which increases the risk of gastrointestinal bleeding (GIB). This study aims to assess the incidence, etiology, and outcomes of GIB within one year post-PCI at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. This retrospective analysis included 435 patients who underwent PCI at SQUH between January and December 2017, excluding those with multiple PCI procedures and incomplete data. GIB was defined using the thrombolysis in myocardial infarction (timi) bleeding score. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY) with binary logistic regression employed to identify significant risk factors for GIB. A p-value < 0.05 was considered statistically significant. GIB was identified in 15 patients (age 67.8 ± 8.8 years; 60% male), resulting in an incidence within one year post-PCI of 3.4%. Melena (53.3%) and hematemesis (20.0%) were the most frequent clinical presentations, with peptic ulcer disease being the predominant underlying etiology (40%). Significant risk factors included advanced age, chronic kidney disease, pre-existing peptic ulcer disease, and the use of non-steroidal anti-inflammatory drugs. The incidence of GIB observed in this study aligns with previously reported rates. These findings highlight the importance of pre-PCI risk stratification for bleeding, especially in high-risk patients. Prophylactic measures, such as the use of gastric protective agents, should be considered to mitigate the risk of GIB in patients undergoing PCI.

GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register

To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry

BackgroundThe DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). ObjectiveTo compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. MethodsWe included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. ResultsA total of 2834 AF patients (median age [IQR] 69 [62–77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55–0.70; DOAC score AUC 0.62, 95 % CI 0.59–0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. ConclusionIn a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.

Cerebral collaterals are associated with pre-treatment brain-blood barrier permeability in acute ischemic stroke patients.

To investigate the relationship between collaterals and blood-brain barrier (BBB) permeability on pre-treatment MRI in a cohort of acute ischemic stroke (AIS) patients treated with thrombectomy. We conducted a retrospective analysis of the HIBISCUS-STROKE cohort, a single-center observational study that enrolled patients treated with thrombectomy from 2016 to 2022. Dynamic-susceptibility MRIs were post-processed to generate K2 maps with arrival-time correction, which were co-registered with apparent diffusion coefficient (ADC) maps. The 90th percentile of K2 was extracted from the infarct core-defined by an ADC ≤ 620 × 10-6 mm2/s with manual adjustments-and expressed as a percentage change compared to the contralateral white matter. Collaterals were assessed using pre-thrombectomy digital subtraction arteriography with an ASITN/SIR score < 3 defining poor collaterals. Out of 249 enrolled, 101 (40.6%) were included (median age: 72.0 years, 52.5% of males, median NIHSS score at admission: 15.0). Patients with poor collaterals (n = 44) had worse NIHSS scores (median: 16.0 vs 13.0, p = 0.04), larger infarct core volumes (median: 43.7 mL vs 9.5 mL, p < 0.0001), and higher increases in K2 (median: 346.3% vs 152.7%, p = 0.003). They were less likely to achieve successful recanalization (21/44 vs 51/57, p < 0.0001) and experienced more frequent hemorrhagic transformation (16/44 vs 9/57, p = 0.03). On multiple variable analysis, poor collaterals were associated with larger infarct cores (odds ratio (OR) = 1.12, 95% confidence interval (CI): [1.07, 1.17], p < 0.0001) and higher increases in K2 (OR = 6.63, 95% CI: [2.19, 20.08], p = 0.001). Poor collaterals are associated with larger infarct cores and increased BBB permeability at admission MRI. Poor collaterals are associated with a larger infarct core and increased BBB permeability at admission MRI of AIS patients treated with thrombectomy. These findings may have translational interests for extending thrombolytic treatment eligibility and developing neuroprotective strategies. In AIS, collaterals and BBB disruption have been both linked to hemorrhagic transformation. Poor collaterals were associated with larger ischemic cores and increased BBB permeability on pre-treatment MRI. These findings could contribute to hemorrhagic transformation risk stratification, thereby refining clinical decision-making for reperfusion therapies.

#2302 Bleeding risk stratification following kidney biopsy using “MAJOR BLEEDING RISK SCORE”

Abstract Background and Aims Kidney biopsy (KB) is the gold standard in diagnosing the majority of kidney diseases. While generally KB is a safe procedure, a complication rate of 6-8% has been reported, mainly bleeding. Halimi et al. proposed “The Major Bleeding Risk Score” (MBRS) identifying 11 risk factors (out of a maximum of 41 points) associated with the likelihood of major complications (such bleeding requiring transfusion, arteriography, nephrectomy or death). Method In this retrospective study, we analyzed 358 native KB conducted between 2017 and 2022 by the interventional nephrology team in a tertiary hospital. Following the application of the MBRS, 273 KB were finally included to validate the score within our cohort. Results We analyzed 273 KB, 46.5% were male, with a mean age of 53.6 ± 18.5 years. The majority of KB were performed on the left kidney (82.4%), with an average of 2.1 ± 0.7 cylinders and 12.33 ± 6.27 glomeruli. The MBRS stratified patients into three risk groups: G1 for scores from 0 to 9 points (36.6% KB), G2 for scores between 10 to 19 points (38.8% KB) and G3 for scores from 20 to 29 points (24.5% KB). Eleven patients (4%) had major complications (0.3% in G1, 1.5% in G2 and 2.2% in G3). The risk of bleeding increased proportionally with risk stage (G1 1% vs G2 3.8% vs G3 9%, p=0.037). Patients who experienced a complication after KB had a significantly higher MBRS than patients who did not develop complications (19 ± 5.23 points vs 13 ± 7.19 points, p=0,01). Patients who developed complications associated anaemia, thrombopenia and lower BMI more frequently than patients who did not develop complications (23.6 ± 5.9 vs. 27.3 ± 5.4, p=0.03). The pathology with the highest bleeding was thrombotic microangiopathy [OR 10,54 (2,39-46,51)]. Conclusion The MBRS adequately stratifies patients according to bleeding risk and could be a valuable tool in the clinical practice guiding the decision to proceed with the kidney biopsy.

Bleeding risk stratification in patients admitted for acute coronary syndrome

Abstract Funding Acknowledgements None. Introduction The risk of hemorrhagic events should always be accounted for in patients admitted with acute coronary syndromes (ACS). With the increasing frailty of these patients, it is important to identify them and minimize the risk of such events. Purpose Identify high-risk patients admitted for ACS for hemorrhagic events during their hospital stay. Methods Multicenter retrospective study, data collected from 1/10/2010 and 31/12/2020 with ACS diagnosis. Patients were divided into 3 groups according to hemoglobin (Hb) and platelet (Plat) levels. Group 1 – Hb &amp;lt;8g/dl, Plat &amp;lt;150x109/L; Group 2 – Hb 8-12g/dl, Plat 150-450x109/L; Group 3 – Hb ≥12g/dl, Plat ≥450x109/L. We further divided these patients according to a composite endpoint. Group A without the composite endpoint; Group B with composite endpoint. This composite endpoint was defined as major hemorrhage, intracranial hemorrhage, need of blood transfusions and a Hb decrease of ≥ 2g/dl. Results 19409 patients were enrolled, of those 4707 (24.3%) had the composite endpoint. Group B was older (68±13 vs 66±12, p&amp;lt;0.001), had higher rates of arterial hypertension (72.5% vs 68.2%, p&amp;lt;0.001), diabetes mellitus (35.6% vs 30.7%, p&amp;lt; 0.001), stroke (9.0% vs 6.6%, p &amp;lt; 0.001) and previous haemorrhage (p= 0.004). No statistically significant differences regarding previous MI (p= 0.240). Hb levels &amp;lt;8g/dL (8.1% vs 0.6%, p&amp;lt;0.001) were associated with a higher risk of hemorrhagic events but not lower levels of Plat, instead higher levels (&amp;gt; 450x109/L) were event associated (1.8% vs 0.9%, p&amp;lt;0.001). The choice of femoral access was related to an increased risk of hemorrhagic events (p&amp;lt;0.001). Logistic regression confirmed that the Hb levels &amp;lt; 12g/dL when compared with normal levels were related to the composite endpoint proportionally to the degree of anemia, the lower the level of Hb the more likely these events occur, Hb &amp;lt;8g/dL p&amp;lt;0.001, OR 4.02, CI (95%) 2.50-6.47 and Hb 8-12g/dL, p&amp;lt;0.001, OR 0.761, CI (95%) 0.693-0.837. Survival analysis also showed that cardiovascular (CV) mortality and re-admission at 1 year were related to the degree of anemia. Conclusion Lower levels of Hb correlated well and proportionally to the occurrence of the composite endpoint as well as cardiovascular (CV) mortality and re-admission at 1 year. Contrarily to expected lower levels of Plat did not correlate with a higher risk of hemorrhagic events but instead thrombocytosis did, as a paradoxical risk of bleeding has been noted in patients with thrombocytosis, especially extreme thrombocytosis.

Relative performance evaluation of four bleeding risk scores in atrial fibrillation patients. What does the new DOAC score provide?

BackgroundRecently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. MethodsWe studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. ResultsThere were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively).Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores.In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. ConclusionsThe new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT04364516

BEST-J Score: Validation of a Predicting Model for Delayed Bleeding After Gastric Endoscopic Submucosal Dissection on a European Sample.

Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The BEST-J score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in Western populations. We aimed to validate the BEST-J score on a European sample and to perform a subgroup analysis according to histological classification. Retrospective study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion to 28days after ESD. BEST-J score was calculated in each patient and confronted with the outcome (DB). Final sample included 161 patients. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7days (IQR 6.8). BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC = 0.907 (95%CI 0.801-1.000; p < 0.001). Subgroup analysis by histological classification proved that the discriminative power was still excellent for each grade: low-grade dysplasia-AUC = 0.970 (p < 0.001); high-grade dysplasia-AUC = 0.874 (p < 0.001); early gastric cancer-AUC = 0.881 (p < 0.001). The optimal cut-off value to predict DB was a BEST-J score ≥ 3, which matches the cut-off value for high-risk of bleeding in the original investigation. The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.

A Novel Risk Score for Major Bleeding in Japanese Patients with Non-Valvular Atrial Fibrillation: The J-RISK AF Study.

Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF. Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3). During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores. Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

590 Does Documentation of Postpartum Hemorrhage Risk Stratification Affect Maternal Outcomes?

590 Does Documentation of Postpartum Hemorrhage Risk Stratification Affect Maternal Outcomes?

Predictive Significance of the ABC Score for Early Re-Hemorrhage and In-Hospital Mortality in High-Risk Variceal Bleeding among Cirrhotic Patients

(1) Background: Upper gastrointestinal bleeding due to ruptured varices is a severe complication in patients with cirrhosis, with high rates of recurrent hemorrhage and in-hospital mortality. This study aimed to evaluate the value of the ABC score in predicting two events among 201 cirrhotic patients with high-risk variceal hemorrhage. (2) Methods: The ABC score was calculated and categorized into risk groups of patients, and the association between the ABC score and the rates of early hemorrhagic recurrence and clinic mortality were analyzed. (3) Results: Among 201 patients, 8.0% experienced early rebleeding within five days of admission, and 10.4% died in the hospital. Patients who experienced events had higher average ABC scores compared to those who did not experience these events (p &lt; 0.001), especially in the high-risk group (with ABC score ≥ 8). The ABC score showed an excellent predictive value for in-hospital mortality with an AUROC of 0.804, with the optimal cutoff point being 8 points. Additionally, the ABC score demonstrated an acceptable predictive value for early rebleeding with an AUROC of 0.744, and the best cutoff point was 9 points. (4) Conclusions: The ABC score is closely associated with the rates of early re-hemorrhage and in-hospital mortality in cirrhotic patients with variceal bleeding. This scoring system has the potential for clinical application, aiding in early risk stratification for recurrent bleeding and mortality and allowing for more aggressive interventions in high-risk cases.

Multimodality Platelet Evaluation By Mass Cytometry and Genetic Analysis in Patients with Bleeding Disorders

Introduction: Bleeding disorders are a diverse group of conditions characterized by abnormal bleeding tendencies. Platelet dysfunction is a common underlying cause and although traditional platelet aggregometry is important in the clinical work-up, platelet functional assays often provide limited diagnostic insights, prompting the need for more advanced techniques and approaches. This study aims to explore the utility of mass cytometry combined with genetic analysis in assessing platelet function in patients with otherwise unspecified bleeding tendencies. Methods: In a single-center prospective study, enrolled patients with clinical and laboratory suspicion of platelet-related bleeding disorders were subjected to multimodality evaluation. Mass cytometry (CyTOF) allows for simultaneous evaluation of multiple platelet markers on single cells, including those involved in platelet activation, aggregation, and adhesion, through a panel of heavy metal-conjugated antibodies. Whole genome sequencing with targeted analysis was utilized to identify potential genetic variants associated with quantitative and qualitative platelet disorders and correlated with CyTOF findings. Results: CyTOF revealed altered platelet markers associated with activation, aggregation, and adhesion in 40% (n=14) of total participants (n=35) with suspected platelet-related bleeding disorders ( Table 1). CyTOF showed significant concordance with platelet aggregometry in 74% of participants (data not shown). Alterations in specific CyTOF markers (e.g., PAC-1, CD40L) correlated with bleeding risk by univariate analysis of patients stratified to high vs low risk groups based on ISTH bleeding assessment tool (ISTH-BAT) ( Table 1). Multivariate analysis using a random forest machine learning algorithm identified variables most predictive of bleeding risk, including CD40L, PAC-1, P-selectin, and mean platelet volume. Genetic analysis identified one or more variants in genes implicated in qualitative and quantitative platelet disorders in 61% (n=19) of total patients analyzed ( Figure 1). Abnormal CyTOF findings were associated with greater proportion of variants detected (79% with abnormal CyTOF vs 53% with normal CyTOF) ( Figure 1). Direct associations between specific mass cytometry findings and genetic variants (i.e., GPIIb, GPIIIa, GPIb, GPIX, etc.) were discovered for several patients, providing important information in evaluating variant pathogenicity and diagnostic validation. Conclusion: This study highlights the potential of integrating mass cytometry and genetic analysis to assist in the diagnosis of otherwise unspecified bleeding tendencies, bleeding risk stratification, and patient management. Our findings enhance the understanding of platelet function in patients with bleeding disorders and provide valuable insights into the complex relationship between platelet phenotypes and genetic determinants. Further investigations with a larger patient cohort are warranted to validate and expand upon these initial correlations and explore their clinical implications in diagnosis and management of bleeding disorders.

High bleeding risk mainly predicts non-access site bleeding events in the first month after percutaneous coronary intervention

Abstract Background/Introduction The majority of bleeding events after percutaneous coronary intervention (PCI) occur in the first month after PCI. To predict and anticipate on events during hospitalisation and in the first month, the CRUSADE- and ACUITY scores have been developed. In order to enhance the use of bleeding risk stratification, a consortium of PCI centres in the South East of the Netherlands has created and implemented a simple binary variant of the existing models. High bleeding risk (HBR) is defined by one of the following: eGFR&amp;lt; 30; anaemia (Hb &amp;lt; 7mmol/L); a spontaneous bleeding within one year before PCI; a history of intracranial haemorrhage. Purpose We evaluated the predictive value of our risk model and other risk factors for bleeding events in the first month after PCI and discriminated between access site- non-access site bleedings. Methods In an ongoing multicentre prospective PCI registry in the South East of the Netherlands collects baseline and follow-up data of all patients undergoing PCI. We compared access site- and non- access site bleedings between HBR and non HBR using the Kaplan Meier method and Cox regression. Also, we performed multivariate analysis of the separate factors of the model and other probable risk factors. Results We collected baseline and 30 day follow-up data in 3996 patients of which 357 with HBR (9%). Access site bleedings occurred in 3% of patients with HBR vs 2% without (sens. 0.13; spec. 0.98). Patients with HBR showed 5% non-access site bleedings versus 1% in non HBR (sens. 0.21; spec. 0.99). Survival curves and hazard ratios presented in figure 1 show that these differences are significant only for non-access site bleedings (HR: 4.2, 95% CI: 2.47-7.30). The multivariate analysis is presented in table 1. All bleeding events were predicted by age ≥ 60 and peripheral arterial disease. Furthermore, non-access site bleedings were predicted by anaemia and bleeding events in the previous year. Additional risk factors for access site bleedings were female sex and double access site punction. Conclusion The simplified risk model showed to be conservative in the determination of HBR as depicted by the sensitivity and specificity. However, it showed good discriminative value for non-access site bleedings which was driven by anemia and a history of bleedings. Furthermore, these results suggest that age ≥60 and peripheral arterial disease should be taken into consideration. Extra precaution for access site bleedings should also be taken in female patients and in the case of double access site punction.Figure 1Table 1

Parsimonious versus extensive score: can we simplify bleeding risk stratification after percutaneous coronary intervention without losing specificity?

Abstract Background/Introduction Prediction of bleeding risk in patients receiving dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has been repeatedly attempted and resulted in multiple risk models. To promote the adoption and use of risk stratification among clinicians, a consortium in the South East of the Netherlands, the "ZON-HR", has created a simple binary variant of the existing logistic models. This model includes commonly available factors which can be incorporated into the PCI report to generate stratification. In this "parsimonious" model, high bleeding risk (HBR) is stratified according to: history of intracranial haemorrhage, previous spontaneous bleeding, Hb &amp;lt; 11 g/dL, eGFR&amp;lt; 30. Purpose We aimed to perform an external validation of our model for bleeding risk and to demonstrate its discriminative value in comparison with the PRECISE DAPT score, an acknowledged risk score. Methods We performed a post hoc analysis of the GLOBAL LEADERS trial, a multicenter randomized trial, comparing ticagrelor monotherapy after one month of DAPT with standard DAPT after PCI. We stratified the patients for HBR according to the ZON-HR or a PRECISE-DAPT score ≥ 25. Bleeding events one year after PCI were compared in the entire population and in subgroups for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), Ticagrelor monotherapy and DAPT. Results Of the 15968 patients included in GLOBAL LEADERS, 1059 patients were excluded due to missing variables required for either model. Among the 14909 patients, 17% had HBR according to the PRECISE DAPT score, 4% according to ZON-HR and 3% according to both. Bleeding events occurred in 8.5% and 13% of HBR defined by PRECISE DAPT or ZON-HR respectively. Patients with HBR according to both models showed 13% bleedings as opposed to 5% in non-HBR. Table 1 presents the sensitivity and specificity. Regression analysis (figure 1) demonstrated that patients with HBR according to either model have significantly more bleedings. This was also significant in all subgroups except for ACS patients receiving standard DAPT when the ZON-HR model was used. Conclusion The ZON-HR model is more conservative compared to the PRECISE DAPT score as depicted by the sensitivity and specificity. This can be explained by the larger number of risk factors used in the PRECISE DAPT score that cumulatively contributes to the sensitivity as opposed to the binary ZON-HR model which is more specific. However, the survival curves and hazard ratios showed good predictive value of both models for bleeding risk in the overall population.Table 1.Figure 1.

Abstract 14598: Predictive Value of the High Bleeding Risk Criteria of the Academic Research Consortium in Black and White Individuals

Introduction: The High Bleeding Risk (HBR) criteria of the Academic Research Consortium (ARC) are a valuable tool for bleeding risk stratification in White and Asian patients undergoing percutaneous coronary intervention (PCI). Hypothesis: The predictive value of the ARC-HBR criteria may vary in Black patients. Methods: Patients who underwent PCI at a large tertiary-care center from 2012 to 2019 who self-reported as non-Hispanic White or Black were included and stratified in HBR and no-HBR based on the ARC-HBR definition. The primary outcome was major bleeding (according to a study specific definition) at 1 year after PCI; secondary outcomes included post-discharge major bleeding, all-cause death and myocardial infarction (MI). Results: Among 9462 patients, 1881 (19.9%) identified as Black and 7581 (80.1%) as White. In these two groups, the HBR criteria were met by 50.8% and 45.6% of patients, respectively, and the frequency of each individual ARC-HBR criterion differed (Figure 1). HBR was associated with a consistent higher risk of major bleeding in Black (7.8% vs. 3.5%, adj. HR 2.02, 95% CI 1.29-3.17) and White patients (7.5% vs. 2.7%, adj. HR 2.49, 95% CI 1.95-3.18, interaction p-value 0.451) (Figure 1). The HBR-related risk of post-discharge bleeding tended to be higher in Black patients (adj. HR 1.67, 95% CI 0.84-3.33) and was significantly increased in White patients (adj HR 3.09, 95% 2.06-4.64, interaction p-value 0.341). All-cause death and MI were increased in HBR patients consistently in the Black and the White group. The predictive value of the ARC-HBR criteria for major bleeding and post-discharge bleeding was good in both Black (0.72 and 0.74, respectively) and White (0.70 and 0.68, respectively). Conclusions: In Black and White patients undergoing PCI, the ARC-HBR criteria were differently distributed and had a good predictive value for major bleeding in both groups.

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.